The Gale Encyclopedia of Neurological Disorders vol 1 - part 2 doc

Alzheimer disease (NSAIDs) are currently being investigated for their use in treating patients with Alzheimer disease Coping with the disorder There are strategies to cope with this disorder and these should be considered in the beginning stages of the disease Coping mechanisms depend on whether there are family members available for support If an individual is without family members, relying on community support through neighbors or volunteers of Alzheimer disease organizations will be necessary Many precautions can be made early on to avoid difficult or life-threatening situations later, while maintaining everyday activities in the home environment Dealing with a person with Alzheimer disease with patience is important Daily tasks should be performed when the person with Alzheimer disease feels best Informing neighbors of the person’s condition is an important first step Arranging for assistance, depending on the stage of the disorder, will become necessary As the ability to drive may be compromised fairly early in the disorder, transportation may need to be arranged There are local chapters of the Alzheimer’s Association that offer help with transportation requirements In the early period of the disease when memory loss is minimal, it is helpful for family and friends to interact with the affected person, reminding him or her to take medication, eat, keep appointments, and so forth Family and friends can help sustain the Alzheimer patient’s daily living activities Keeping records is also helpful, particularly if several people are overseeing the patient’s care Additionally, organizing the household so that it is easy to find important items is recommended Other helpful coping mechanisms include posting signs to remind patients of important phone numbers, to turn off appliances, and to lock doors It is important that all electrical cords and appliances are arranged to minimize distraction, and to prevent danger of falling or misuse Assistance in handling finances is usually necessary Providing an extra house key for neighbors and setting up a schedule to check on persons with Alzheimer disease is very helpful for both the patient and the family By utilizing these and other family, neighborhood, and community resources, many people with early Alzheimer disease are able to maintain a successful lifestyle in their home environment for months or years Recovery and rehabilitation For a person with Alzheimer disease, emphasis is placed on maintaining cognitive and physical function for as long as possible Currently, there is no cure for 38 Alzheimer and, once the symptoms develop, patients not recover Instead, they progressively worsen, usually over a period of years This has many psychosocial and financial ramifications for the patient and the patient’s caretakers Social service workers can help families plan for long-term care, as persons with Alzheimer disease most often eventually require 24-hour assistance with feeding, toileting, bathing, personal safety, and social interaction Taking care of patients in the later stages can be financially and psychologically draining Various support systems are available through community mental health centers and national support organizations Clinical trials There are currently many clinical trials for the treatment or prevention of Alzheimer disease sponsored by the National Institutes of Health (NIH) Large multi-center clinical trials such as a Phase III clinical trail are aimed at determining whether anti-inflammatory drugs delay agerelated cognitive decline (Contact information: UCLA Neuropsychiatric Institute, Los Angeles, California, 90024 Recruiter: Andrea Kaplan, (310) 825-0545 or her email: akaplan@mednet.ucla.edu.) A Phase III clinical trial is also organized to test the drug Risperidone for the treatment of agitated behavior in Alzheimer’s patients (Contact information: Palo Alto Veterans Administration Health Care System, Menlo Park, California, 94025 Recruiter: Erin L Cassidy, PhD, (650) 493-5000, ext.27013 or her email: ecassidy@stanford.edu.) Other trials include: • A study on Valproate to prevent cognitive and behavioral symptoms in patients Contact information: Laura Jakimovich, RN, MS, (585) 760-6578 or her email: laura_jakimovich@urmc.rochester.edu • The drug Simvastatin, a cholesterol-lowering medication, is being studied to learn if it slows the progression of Alzheimer disease Contact information: Stanford University, Palo Alto, California, 94304 Recruiter: Lisa M Kinoshita, PhD, (650) 493-0571 or her email: lisakino@stanford.edu • A study of the efficacy and dose of the drug NS 2330 to improve cognition Contact information: Peter Glassman, MD, PhD, (800) 344-4095, ext 4776 or his email: pglassma@rdg.boehringer-ingelheim.com • A study of investigational medications for the treatment of Alzheimer patients Contact information: Eli Lilly and Company, (877) 285-4559 There are also many other studies that are investigating various other pharmacological agents such as vitamin E and other currently available drugs GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS There is considerable variability in the rate of Alzheimer disease progression The Alzheimer Disease Association claims that the time from the onset of clinical symptoms to death can range from three to 20 years, with an average duration of eight years There are probably many environmental and genetic factors that play a role in the progression of the disease The accumulation of damage and loss of brain cells eventually results in the failure of many different organ systems in the body According to the National Institute of Neurological Disorders and Stroke, the most common cause of death is due to infection Special concerns Alzheimer disease should be distinguished from other forms of dementia In some cases, depression can result in dementia-like symptoms Other examples include chronic drug use, chronic infections of the central nervous system, thyroid disease, and vitamin deficiencies These causes of dementia can often be treated It is, therefore, important to obtain an accurate diagnosis to avoid complications associated with the inappropriate treatment and long-term care of these patients There are also several genetically based syndromes in which dementia plays a role Genetic counseling Genetic counseling is important for family members biologically related to patients with Alzheimer disease because each first-degree relative has as much as a 20% lifetime risk of also being affected The risk to immediate relatives increases as more family members develop the disease In the early-onset form of the disease, the inheritance pattern is thought to be autosomal dominant This means that a carrier (who will eventually be affected) has a 50% chance of passing on the mutated gene to his or her offspring The general consensus in the scientific and medical community is to not test children or adolescents in the absence of symptoms for adult-onset disorders There are many problems associated with predictive testing of asymptomatic individuals who are not yet adults Children who undergo predictive testing lose the choice later in life (when they are capable of understanding the full ramifications of the disease) to know or not to know this information It is, therefore, an important consideration that involves ethical and psychological implications Resources BOOKS Franci, E Daunwald, and K J Isrelbacher New York: McGraw Hill, 2001 Castleman, Michael, et al There’s Still a Person in There: The Complete Guide to Treating and Coping with Alzheimer’s New York: Perigee Books, 2000 Mace, Nancy L., and Peter V Rabins The 36-Hour Day: A Family Guide to Caring for Persons with Alzheimer Disease, Related Dementing Illnesses, and Memory Loss in Later Life New York: Warner Books, 2001 PERIODICALS Campion, D., et al “Early-onset Autosomal Dominant Alzheimer Disease: Prevalence, Genetic Heterogeneity, and Mutation Spectrum.” Am J Hum Genet 65 (1999): 664–70 Green, R.C “Risk Assessment for Alzheimer’s Disease with Genetic Susceptibility Testing: Has the Moment Arrived?” Alzheimer’s Care Quarterly (2002): 3,208–14 Rogan, S., and C F Lippa “Alzheimer’s Disease and Other Dementias: A Review.” Am J Alzheimers Dis Other Demen (2002) 17: 11–7 Romas, S N., et al “Familial Alzheimer Disease among Caribbean Hispanics: A Reexamination of Its Association with APOE.” Arch Neurol (2002) 59: 87–91 Rosenberg, R N “The Molecular and Genetic Basis of AD: The End of the Beginning: The 2000 Wartenberg Lecture.” Neurology 54 (2000): 2045–54 OTHER ADEAR Alzheimer Disease Education and Referral Center National Institute on Aging about Alzheimer’s Disease— General Information February 10, 2004 (March 30, 2004) National Institutes of Health Alzheimer’s Disease February 10, 2004 (March 30, 2004) National Library of Medicine Alzheimer’s Disease MEDLINE plus Health Information February 10, 2004 (March 30, 2004) ORGANIZATIONS Alzheimer’s Association 919 North Michigan Avenue, Suite 1000, Chicago, IL 60611-1676 (312) 335-8700 or (800) 272-3900; Fax: (312) 335-1110 info@alz.org Alzheimer’s Education and Referral Center PO Box 8250, Silver Springs, MD 20907-8250 (800) 438-4380 adear@alzheimers.org National Institute on Aging Building 31, Room 5C27, 31 Center Drive, MSC 2292, Bethesda, MD 20892 (301) 496-1752 Bird, T D “Memory Loss and Dementia.” In Harrison’s Principles of Internal Medicine, 15th ed Edited by A S GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Bryan Richard Cobb, PhD 39 Alzheimer disease Prognosis Amantadine S Amantadine Key Terms Definition Amantadine is a synthetic antiviral agent that also has strong antiparkinsonian properties It is sold in the United States under the brand name Symmetrel, and is also available under its generic name Purpose Amantadine is used to treat a group of side effects, called parkinsonian side effects, that include tremors, difficulty walking, and slack muscle tone These side effects may occur in patients who are taking antipsychotic medications used to treat mental disorders such as schizophrenia An unrelated use of amantadine is in the treatment of viral infections of some strains of influenza A Description Some medicines, called antipsychotic drugs, that are used to treat schizophrenia and other mental disorders can cause side effects similar to the symptoms of Parkinson’s disease The patient does not have Parkinson’s disease, but may experience shaking in muscles while at rest, difficulty with voluntary movements, and poor muscle tone These symptoms are similar to the symptoms of Parkinson’s disease One way to eliminate these undesirable side effects is to stop taking the antipsychotic medicine Unfortunately, the symptoms of the original mental disorder usually come back; in most cases, simply stopping the antipsychotic medication is not a reasonable option Some drugs such as amantadine that control the symptoms of Parkinson’s disease also control the parkinsonian side effects of antipsychotic medicines Amantadine works by restoring the chemical balance between dopamine and acetylcholine, two neurotransmitter chemicals in the brain Taking amantadine along with the antipsychotic medicine helps to control symptoms of the mental disorder, while reducing parkinsonian side effects Amantadine is in the same family of drugs commonly known as anticholinergic drugs, including biperiden and trihexyphenidyl Recommended dosage Amantadine is available in 100 mg tablets and capsules, as well as a syrup containing 50 mg of amantadine in each teaspoonful For the treatment of drug-induced parkinsonian side effects, amantadine is usually given in a dose of 100 mg orally twice a day Some patients may need a total daily dose as high as 300 mg Patients who are 40 Acetylcholine A naturally occurring chemical in the body that transmits nerve impulses from cell to cell It causes blood vessels to dilate, lowers blood pressure, and slows the heartbeat Anticholinergic Related to the ability of a drug to block the nervous system chemical acetylcholine Dopamine A chemical in brain tissue that serves to transmit nerve impulses (a neurotransmitter) and helps to regulate movement and emotions Neurotransmitter A chemical in the brain that transmits messages between neurons, or nerve cells Parkinsonian Related to symptoms associated with Parkinson’s disease, a nervous system disorder characterized by abnormal muscle movement of the tongue, face, and neck; inability to walk or move quickly; walking in a shuffling manner; restlessness; and/or tremors taking other antiparkinsonian drugs at the same time may require lower daily doses of amantadine (e.g., 100 mg daily) People with kidney disease or who are on hemodialysis must have their doses lowered In these patients, doses may range from 100 mg daily to as little as 200 mg every seven days Precautions Amantadine increases the amount of the dopamine (a central nervous system stimulant) in the brain Because of this, patients with a history of epilepsy or other seizure disorders should be carefully monitored while taking this drug This is especially true in the elderly and in patients with kidney disease Amantadine may cause visual disturbances and affect mental alertness and coordination People should not operate dangerous machinery or motor vehicles while taking this drug Side effects Five to 10% of patients taking amantadine may experience nervous system side effects, including: • dizziness or lightheadedness • insomnia GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS • impaired concentration DeVane, C Lindsay, PharmD “Drug Therapy for Psychoses.” In Fundamentals of Monitoring Psychoactive Drug Therapy Baltimore: Williams and Wilkins, 1990 One to 5% of patients taking amantadine may experience other nervous system side effects, including: • irritability or agitation • depression Jack Raber, PharmD Ambenonium see Cholinergic stimulants • confusion • sleepiness or nightmares S Amnestic disorders • fatigue Definition • lack of coordination • headache In addition, up to 1% of patients may experience hallucinations, euphoria (excitement), extreme forgetfulness, aggressive behavior, personality changes, or seizures Seizures are the most serious of all the side effects associated with amantadine Gastrointestinal side effects may also occur in patients taking amantadine Five to 10% of people taking this drug experience nausea and up to 5% have dry mouth, loss of appetite, constipation, and vomiting In most situations, amantadine may be continued and these side effects treated symptomatically One to 5% of patients taking amantadine have also reported a bluish coloring of their skin (usually on the legs) that is associated with enlargement of the blood vessels (livedo reticularis) This side effect usually appears within one month to one year of starting the drug and subsides within weeks to months after the drug is discontinued People who think they may be experiencing this or other side effects from any medication should tell their physician Interactions Taking amantadine along with other drugs used to treat parkinsonian side effects may cause increased confusion or even hallucinations The combination of amantadine and central nervous system stimulants (e.g., amphetamines or decongestants) may cause increased central nervous stimulation or increase the likelihood of seizures Resources BOOKS American Society of Health-System Pharmacists AHFS Drug Information 2002 Bethesda: American Society of HealthSystem Pharmacists, 2002 Amnestic disorders are conditions that cause memory loss Description Memory is the ability to retain and recall new information Memory can be subdivided into short-term memory, which involves holding onto information for a minute or less, and long-term memory, which involves holding onto information for over a minute Long-term memory can be further subdivided into recent memory, which involves new learning, and remote memory, which involves old information In general, amnestic disorders more frequently involve deficits in new learning or recent memory There are a number of terms that are crucial to the understanding of amnestic disorders In order to retain information, an individual must be able to pay close enough attention to the information that is presented; this is referred to as registration The process whereby memories are established is referred to as encoding or storage Retaining information in the long-term memory requires passage of time during which memory is consolidated When an individual’s memory is tested, retrieval is the process whereby the individual recalls the information from memory Working memory is the ability to manipulate information from short-term memory in order to perform some function Amnestic disorders may affect any or all of these necessary steps The time period affecting memory is also described Anterograde amnesia is more common Anterograde amnesia begins at a certain point in time and continues to interfere with the establishment of memory from that point forward in time Retrograde amnesia refers to a loss of memory for information that was learned prior to the onset of amnesia Retrograde amnesia often occurs in conjunction with head injury, and may result in erasure of memory of events or information from some time period (ranging from seconds to months) prior to the head injury Over the course of recovery and rehabilitation from a head GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 41 Amnestic disorders • nervousness or anxiety Amnestic disorders Key Terms Acetylcholine A brain chemical or neurotransmitter that carries information throughout the nervous system Anterograde Memory loss for information/events occurring after the onset of the amnestic disorder Delirium A condition characterized by waxingand-waning episodes of confusion and agitation Dementia A chronic condition in which thinking and memory are progressively impaired Other symptoms may also occur, including personality changes and depression Retrograde Memory loss for information/events prior to the onset of the amnestic disorder Transient ischemic attack (TIA) A stroke-like phenomenon in which a brief blockage of a brain blood vessel causes short-term neurological deficits that are completely resolved within 24 hours of their onset injury, memory may be restored or the period of amnesia may eventually shorten Demographics About 7% of all individuals over the age of 65 have some form of dementia that involves some degree of amnesia, as about 50% of all individuals over the age of 85 Causes and symptoms A number of brain disorders can result in amnestic disorders, including various types of dementia (such as Alzheimer’s disease), traumatic brain injury (such as concussion), stroke, accidents that involve oxygen deprivation to the brain or interruption of blood flow to the brain (such as ruptured aneurysms), encephalitis, tumors in the thalamus and/or hypothalamus, Wernicke-Korsakoff syndrome (a sequelae of thiamine deficiency usually due to severe alcoholism), and seizures Psychological disorders can also cause a type of amnesia called “psychogenic amnesia.” A curious condition called transient global amnesia causes delirium (a period of waxing and waning confusion and agitation), anterograde amnesia, and retrograde amnesia for events and information from the several hours prior to the onset of the attack Transient global amnesia usually only lasts for several hours Ultimately, the individual recovers completely, with no lasting memory 42 Hippocampus Amygdala Memory loss may result from bilateral damage to the limbic system of the brain responsible for memory storage, processing, and recall (Illustration by Electronic Illustrators Group.) deficit The cause of transient global amnesia is poorly understood; researchers are suspicious that it may be due to either seizure activity in the brain or a brief blockage in a brain blood vessel, which causes a brief stroke-like event that completely resolves without permanent sequelae (similar to a transient ischemic attack) Symptoms of amnestic disorders may include difficulty recalling remote events or information, and/or difficulty learning and then recalling new information In some cases, the patient is fully aware of the memory impairment, and frustrated by it; in other cases, the patient may seem completely oblivious to the memory impairment or may even attempt to fill in the deficit in memory with confabulation Depending on the underlying condition responsible for the amnesia, a number of other symptoms may be present as well Diagnosis Diagnosis of amnestic disorders begins by establishing an individual’s level of orientation to person, place, and time Does he or she know who he or she is? Where he or she is? The day/date/time? An individual’s ability to recall common current events (who is the president?) may reveal information about the memory deficit A family member or close friend may be an invaluable part of the examination, in order to provide some background information on the onset and progression of the memory loss, GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS A variety of memory tests can be utilized to assess an individual’s ability to attend to information, utilize shortterm memory, and store and retrieve information from long-term memory Both verbal and visual memory should be tested Verbal memory can be tested by working with an individual to memorize word lists, then testing recall after a certain amount of time has elapsed Similarly, visual memory can be tested by asking an individual to locate several objects that were hidden in a room in the individual’s presence Depending on what types of conditions are being considered, other tests may include blood tests, neuroimaging (CT, MRI, or PET scans of the brain), cerebrospinal fluid testing, and EEG testing Treatment team A neurologist and/or psychiatrist may be involved in diagnosing and treating amnestic disorders Depending on the underlying condition responsible for the memory deficit, other specialists may be involved as well Occupational and speech and language therapists may be involved in rehabilitation programs for individuals who have amnestic disorders as part of their clinical picture remove the tumor Individuals with transient global amnesia can be expected to fully recover from their memory impairment within hours or days of its onset In the case of some traumatic brain injuries, the amnesia may improve with time (as brain swelling decreases, for example), but there may always remain some degree of amnesia for the events just prior to the moment of the injury Resources BOOKS Cummings, Jeffrey L “Disorders of Cognition.” In Cecil Textbook of Internal Medicine, edited by Lee Goldman, et al Philadelphia: W B Saunders Company, 2000 Gabrieli, John D., et al “Memory.” In Textbook of Clinical Neurology, edited by Christopher G Goetz Philadelphia: W B Saunders Company, 2003 Mesulam, M.-Marsel “Aphasias and Other Focal Cerebral Disorders.” In Harrison’s Principles of Internal Medicine, edited by Eugene Braunwald, et al New York: McGrawHill Professional, 2001 Rosalyn Carson-DeWitt, MD Amphetamine see Central nervous system stimulants Treatment In some cases, treatment of the underlying disorder may help improve the accompanying amnesia In mild cases of amnesia, rehabilitation may involve teaching memory techniques and encouraging the use of memory tools, such as association techniques, lists, notes, calendars, timers, etc Memory exercises may be helpful Recent treatments for Alzheimer’s disease and other dementias have involved medications that interfere with the metabolism of the brain chemical (neurotransmitter) called acetylcholine, thus increasing the available quantity of acetylcholine These drugs, such as donepezil and tacrine, seem to improve memory in patients with Alzheimer’s disease Research studies are attempting to explore whether these drugs may also help amnestic disorders that stem from other underlying conditions Prognosis The prognosis is very dependent on the underlying condition that has caused the memory deficit, and on whether that condition has a tendency to progress or stabilize Alzheimer’s disease, for example, is relentlessly progressive, and therefore the memory deficits that accompany this condition can be expected to worsen considerably over time Individuals who have memory deficits due to a brain tumor may have their symptoms improve after surgery to S Amyotrophic lateral sclerosis Definition Amyotrophic lateral sclerosis (ALS) is a disease that breaks down tissues in the nervous system (a neurodegenerative disease) of unknown cause that affects the nerves responsible for movement It is also known as motor neuron disease and Lou Gehrig’s disease, after the baseball player whose career it ended Description ALS is a disease of the motor neurons, those nerve cells reaching from the brain to the spinal cord (upper motor neurons) and the spinal cord to the peripheral nerves (lower motor neurons) that control muscle movement In ALS, for unknown reasons, these neurons die, leading to a progressive loss of the ability to move virtually any of the muscles in the body ALS affects “voluntary” muscles, those controlled by conscious thought, such as the arm, leg, and trunk muscles ALS, in and of itself, does not affect sensation, thought processes, the heart muscle, or the “smooth” muscle of the digestive system, bladder, and other internal organs Most people with ALS retain function of their eye muscles as well However, various forms GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 43 Amyotrophic lateral sclerosis as well as information regarding the individual’s original level of functioning Amyotrophic lateral sclerosis Key Terms Aspiration Inhalation of food or liquids into the lungs Bulbar muscles Muscles of the mouth and throat responsible for speech and swallowing Fasciculations Involuntary twitching of muscles Motor neuron A nerve cell that controls a muscle Riluzole (Rilutek) The first drug approved in the United States for the treatment of ALS Voluntary muscle A muscle under conscious control; contrasted with smooth muscle and heart muscle, which are not under voluntary control of ALS may be associated with a loss of intellectual function (dementia) or sensory symptoms “Amyotrophic” refers to the loss of muscle bulk, a cardinal sign of ALS “Lateral” indicates one of the regions of the spinal cord affected, and “sclerosis” describes the hardened tissue that develops in place of healthy nerves ALS affects approximately 30,000 people in the United States, with about 5,000 new cases each year It usually begins between the ages of 40 and 70, although younger onset is possible Men are slightly more likely to develop ALS than women ALS progresses rapidly in most cases It is fatal within three years for 50% of all people affected, and within five years for 80% Ten percent of people with ALS live beyond eight years Causes and symptoms Causes The symptoms of ALS are caused by the death of motor neurons in the spinal cord and brain Normally, these neurons convey electrical messages from the brain to the muscles to stimulate movement in the arms, legs, trunk, neck, and head As motor neurons die, the muscles they enervate cannot be moved as effectively, and weakness results In addition, lack of stimulation leads to muscle wasting, or loss of bulk Involvement of the upper motor neurons causes spasms and increased tone in the limbs, and abnormal reflexes Involvement of the lower motor neurons causes muscle wasting and twitching (fasciculations) Although many causes of motor neuron degeneration have been suggested for ALS, none has yet been proven responsible Results of recent research have implicated toxic 44 molecular fragments known as free radicals Some evidence suggests that a cascade of events leads to excess free radical production inside motor neurons, leading to their death Why free radicals should be produced in excess amounts is unclear, as is whether this excess is the cause or the effect of other degenerative processes Additional agents within this toxic cascade may include excessive levels of a neurotransmitter known as glutamate, which may over-stimulate motor neurons, thereby increasing free-radical production, and a faulty detoxification enzyme known as SOD-1, for superoxide dismutase type The actual pathway of destruction is not known, however, nor is the trigger for the rapid degeneration that marks ALS Further research may show that other pathways are involved, perhaps ones even more important than this one Autoimmune factors or premature aging may play some role, as could viral agents or environmental toxins Two major forms of ALS are known: familial and sporadic Familial ALS accounts for about 10% of all ALS cases As the name suggests, familial ALS is believed to be caused by the inheritance of one or more faulty genes About 15% of families with this type of ALS have mutations in the gene for SOD-1 SOD-1 gene defects are dominant, meaning only one gene copy is needed to develop the disease Therefore, a parent with the faulty gene has a 50% chance of passing the gene along to a child Sporadic ALS has no known cause While many environmental toxins have been suggested as causes, to date no research has confirmed any of the candidates investigated, including aluminum and mercury and lead from dental fillings As research progresses, it is likely that many cases of sporadic ALS will be shown to have a genetic basis as well A third type, called Western Pacific ALS, occurs in Guam and other Pacific islands This form combines symptoms of both ALS and Parkinson’s disease Symptoms The earliest sign of ALS is most often weakness in the arms or legs, usually more pronounced on one side than the other at first Loss of function is usually more rapid in the legs among people with familial ALS and in the arms among those with sporadic ALS Leg weakness may first become apparent by an increased frequency of stumbling on uneven pavement, or an unexplained difficulty climbing stairs Arm weakness may lead to difficulty grasping and holding a cup, for instance, or loss of dexterity in the fingers Less often, the earliest sign of ALS is weakness in the bulbar muscles, those muscles in the mouth and throat that control chewing, swallowing, and speaking A person with bulbar weakness may become hoarse or tired after speaking at length, or speech may become slurred GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Normal nerve fiber Amyotrophic lateral sclerosis NORMAL SPINAL NEURON DISEASED SPINAL NEURON Affected nerve fiber Normal skeletal muscle Wasted skeletal muscle Amyotrophic lateral sclerosis (ALS) is caused by the degeneration and death of motor neurons in the spinal cord and brain These neurons convey electrical messages from the brain to the muscles to stimulate movement in the arms, legs, trunk, neck, and head As motor neurons degenerate, the muscles are weakened and cannot move as effectively, leading to muscle wasting (Illustration by Electronic Illustrators Group.) In addition to weakness, the other cardinal signs of ALS are muscle wasting and persistent twitching (fasciculation) These are usually seen after weakness becomes obvious Fasciculation is quite common in people without the disease, and is virtually never the first sign of ALS While initial weakness may be limited to one region, ALS almost always progresses rapidly to involve virtually all the voluntary muscle groups in the body Later symptoms include loss of the ability to walk, to use the arms and hands, to speak clearly or at all, to swallow, and to hold the head up Weakness of the respiratory muscles makes breathing and coughing difficult, and poor swallowing control increases the likelihood of inhaling food or saliva (aspiration) Aspiration increases the likelihood of lung infection, which is often the cause of death With a ventilator and scrupulous bronchial hygiene, a person with ALS may live much longer than the average, although weakness and wasting will continue to erode any remaining functional abilities Most people with ALS continue to retain function of the extraocular muscles that move their eyes, allowing some communication to take place with simple blinks or through use of a computer-assisted device Diagnosis The diagnosis of ALS begins with a complete medical history and physical exam, plus a neurological examination to determine the distribution and extent of weakness An electrical test of muscle function, called an electromyogram, or EMG, is an important part of the diagnostic process Various other tests, including blood and urine tests, x rays, and CT scans, may be done to rule out other possible causes of the symptoms, such as tumors of GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 45 Amyotrophic lateral sclerosis the skull base or high cervical spinal cord, thyroid disease, spinal arthritis, lead poisoning, or severe vitamin deficiency ALS is rarely misdiagnosed following a careful review of all these factors Treatment There is no cure for ALS, and no treatment that can significantly alter its course There are many things which can be done, however, to help maintain quality of life and to retain functional ability even in the face of progressive weakness As of early 1998, only one drug had been approved for treatment of ALS Riluzole (Rilutek) appears to provide on average a three-month increase in life expectancy when taken regularly early in the disease, and shows a significant slowing of the loss of muscle strength Riluzole acts by decreasing glutamate release from nerve terminals Experimental trials of nerve growth factor have not demonstrated any benefit No other drug or vitamin currently available has been shown to have any effect on the course of ALS A physical therapist works with an affected person and family to implement exercise and stretching programs to maintain strength and range of motion, and to promote general health Swimming may be a good choice for people with ALS, as it provides a low-impact workout to most muscle groups One result of chronic inactivity is contracture, or muscle shortening Contractures limit a person’s range of motion, and are often painful Regular stretching can prevent contracture Several drugs are available to reduce cramping, a common complaint in ALS An occupational therapist can help design solutions to movement and coordination problems, and provide advice on adaptive devices and home modifications Speech and swallowing difficulties can be minimized or delayed through training provided by a speech-language pathologist This specialist can also provide advice on communication aids, including computer-assisted devices and simpler word boards Nutritional advice can be provided by a nutritionist A person with ALS often needs softer foods to prevent jaw exhaustion or choking Later in the disease, nutrition may be provided by a gastrostomy tube inserted into the stomach Mechanical ventilation may be used when breathing becomes too difficult Modern mechanical ventilators are small and portable, allowing a person with ALS to maintain the maximum level of function and mobility Ventilation may be administered through a mouth or nose piece, or through a tracheostomy tube This tube is inserted through a small hole made in the windpipe In addition to 46 providing direct access to the airway, the tube also decreases the risk aspiration While many people with rapidly progressing ALS choose not to use ventilators for lengthy periods, they are increasingly being used to prolong life for a short time The progressive nature of ALS means that most persons will eventually require full-time nursing care This care is often provided by a spouse or other family member While the skills involved are not difficult to learn, the physical and emotional burden of care can be overwhelming Caregivers need to recognize and provide for their own needs as well as those of people with ALS, to prevent depression, burnout, and bitterness Throughout the disease, a support group can provide important psychological aid to affected persons and their caregivers as they come to terms with the losses ALS inflicts Support groups are sponsored by both the ALS Society and the Muscular Dystrophy Association Alternative treatment Given the grave prognosis and absence of traditional medical treatments, it is not surprising that a large number of alternative treatments have been tried for ALS Two studies published in 1988 suggested that amino-acid therapies may provide some improvement for some people with ALS While individual reports claim benefits for megavitamin therapy, herbal medicine, and removal of dental fillings, for instance, no evidence suggests that these offer any more than a brief psychological boost, often followed by a more severe letdown when it becomes apparent the disease has continued unabated However, once the causes of ALS are better understood, alternative therapies may be more intensively studied For example, if damage by free radicals turns out to be the root of most of the symptoms, antioxidant vitamins and supplements may be used more routinely to slow the progression of ALS Or, if environmental toxins are implicated, alternative therapies with the goal of detoxifying the body may be of some use Prognosis ALS usually progresses rapidly, and leads to death from respiratory infection within three to five years in most cases The slowest disease progression is seen in those who are young and have their first symptoms in the limbs About 10% of people with ALS live longer than eight years Prevention There is no known way to prevent ALS or to alter its course GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS BOOKS Adams, Raymond D., Maurice Victor, and Allan H Ropper Adams’ & Victor’s Principles of Neurology, 6th ed New York: McGraw Hill, 1997 Brown, Robert H “The motor neuron diseases.” In Harrison’s Principles of Internal Medicine, 14th ed., edited by Anthony S Fauci, et al., pp 2368-2372 New York: McGraw-Hill, 1998 Feldman, Eva L “Motor neuron diseases.” In Cecil Textbook of Medicine, 21st ed., edited by Lee Goldman and J Claude Bennett, pp 2089-2092 Philadelphia: W B Saunders, 2000 Kimura, Jun, and Ryuji Kaji Physiology of ALS and Related Diseases Amsterdam: Elsevier Science, 1997 Mitsumoto, Hiroshi, David A Chad, Erik Pioro, and Sid Gilman Amyotrophic Lateral Sclerosis New York: Oxford University Press, 1997 Muscular Dystrophy Association 3300 East Sunrise Drive, Tucson, AZ 85718-3208 (520) 529-2000 or (800) 5721717; Fax: (520) 529-5300 WEBSITES ALS Society of Canada ALS Survival Guide American Academy of Family Physicians National Organization for Rare Diseases National Institute of Neurological Disorders and Stroke National Library of Medicine World Federation of Neurology PERIODICALS Ansevin, C F “Treatment of ALS with pleconaril.” Neurology 56, no (2001): 691-692 Eisen, A., and M Weber “The motor cortex and amyotrophic lateral sclerosis.” Muscle and Nerve 24, no (2001): 564-573 Gelanis, D F “Respiratory Failure or Impairment in Amyotrophic Lateral Sclerosis.” Current treatment options in neurology 3, no (2001): 133-138 Ludolph, A C “Treatment of amyotrophic lateral sclerosis— what is the next step?” Journal of Neurology 246, Suppl (2000): 13-18 Pasetti, C., and G Zanini “The physician-patient relationship in amyotrophic lateral sclerosis.” Neurological Science 21, no (2000): 318-323 Robberecht, W “Genetics of amyotrophic lateral sclerosis.” Journal of Neurology 246, Suppl (2000): 2-6 Robbins, R A., Z Simmons, B A Bremer, S M Walsh, and S Fischer “Quality of life in ALS is maintained as physical function declines.” Neurology 56, no (2001): 442-444 ORGANIZATIONS ALS Association of America 27001 Agoura Road, Suite 150, Calabasas Hills, CA 91301-5104 (800) 782-4747 (Information and Referral Service) or (818) 880-9007; Fax: (818) 880-9006 American Academy of Family Physicians 11400 Tomahawk Creek Parkway, Leawood, KS 66211-2672 (913) 9066000 fp@aafp.org American Academy of Neurology 1080 Montreal Avenue, St Paul, Minnesota 55116 (651) 695-1940; Fax: (651) 6952791 info@aan.org American Medical Association, 515 N State Street, Chicago, IL 60610 (312) 464-5000 Centers for Disease Control and Prevention 1600 Clifton Road, Atlanta, GA 30333 (404) 639-3534 or (800) 3113435 , L Fleming Fallon, Jr., MD, DrPH S Anatomical nomenclature Over the centuries, anatomists developed a standard nomenclature, or method of naming anatomical structures Terms such as “up” or “down” obviously have no meaning unless the orientation of the body is clear When a body is lying on its back, the thorax and abdomen are at the same level The upright sense of up and down is lost Further, because anatomical studies and particularly embryological studies were often carried out in animals, the development of the nomenclature relative to comparative anatomy had an enormous impact on the development of human anatomical nomenclature There were obvious difficulties in relating terms from quadrupeds (animals that walk on four legs) who have abdominal and thoracic regions at the same level as opposed to human bipeds in whom an upward and downward orientation might seem more obvious In order to standardize nomenclature, anatomical terms relate to the standard anatomical position When the human body is in the standard anatomical position it is upright, erect on two legs, facing frontward, with the arms at the sides each rotated so that the palms of the hands turn forward In the standard anatomical position, superior means toward the head or the cranial end of the body The term inferior means toward the feet or the caudal end of the body GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 47 Anatomical nomenclature Resources Precautions Diagnosis Migraine headaches are classified by the International Headache Society (IHS) as primary headaches, which means that they are not caused by other diseases or disorders Severely painful headaches, however, are not necessarily migraines and may be caused by other conditions, some of them potentially life-threatening Headaches caused by other disorders are known as secondary headaches They may be associated with space-occupying brain tumors, meningitis, stroke, head trauma, pain referred from the neck or jaw, or a ruptured aneurysm inside the head Patients with any of the following signs or symptoms should be carefully evaluated, including those who have been previously diagnosed with and treated for migraines: severity, and associated symptoms; in addition, people vary in their responses to a given medication It may take some months of trial and error to work out the best treatment regimen for an individual patient with respect to the specific drugs used and their dosage levels Patients should be advised to give each medication a fair trial (usually about two months) before deciding that the drug does not work for them In addition, they should be told that some drugs— particularly the beta-blockers—must be taken for several months before the patient can expect to see results Finally, patients who are taking abortive medications or opioid analgesics should be warned about the risks of dependence or rebound headaches from overuse of these drugs Rebound headaches Rebound headaches are also known as analgesic abuse headaches They result from overuse of abortive drugs, most commonly the ergot alkaloids According to one survey of primary care physicians, about 20% of patients treated for migraine experience rebound headaches These headaches have the following characteristics: • They occur every day or almost every day • The patient is not responding to appropriate treatment for the headaches • They are brought on by a very low level of physical or intellectual activity • The headache is severe and is sudden in onset Although a small percentage of patients with migraines have what are called “crash” or “thunderclap” migraines, most migraine headaches build up slowly over a period of one or two hours • The patient has been using abortive migraine medications more than two days a week • The headache differs from the usual pattern of the patient’s migraines • The patient develops withdrawal symptoms if the medications are stopped abruptly • The patient has described the present headache as “the worst ever.” • The headaches are accompanied by restlessness, depression, irritability, difficulty concentrating, or memory problems • The patient has abnormal neurological signs or symptoms such as a swollen optic disk (papilledema), seeing double, loss of sensation, or alteration of consciousness Some patients may be suffering from another type of primary headache in addition to migraines It is possible, for example, for people to have both chronic tension headaches and migraines, and each type may require separate treatment A third consideration is whether the patient has been diagnosed with any comorbid disorders The doctor must take such conditions as hypertension, depression, epilepsy, heart problems, and other disorders into account when selecting antimigraine medications for the patient Patient education Effective use of antimigraine drugs depends on good communication between the patient and the doctor Migraine headaches vary considerably in their frequency, • The patient has been using the medications above the recommended dosage level Status migrainosus About 40% of all migraine attacks not respond to treatment with triptans or any other medication If the headache lasts longer than 72 hours (a condition known as status migrainosus), the patient may be given narcotic medications to bring on sleep and stop the attack Patients with status migrainosus are often hospitalized because they are likely to be dehydrated from severe nausea and vomiting Special populations CHILDREN Migraines in children are not unusual; a study published in 2003 reported that 10% of children between the ages of six and 20 suffer from migraines, and that they lose, on average, almost two more weeks of school each year than their classmates Treatment of children’s migraines, however, is complicated by the fact that GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 75 Antimigraine medications form Petadolex is sold as soft gelatin 50-mg capsules The recommended dose for migraine prophylaxis is 150 mg daily for adults and 50–100 mg daily for children and adolescents Antimigraine medications most effective medications—whether abortive or prophylactic—have not been adequately evaluated for use in children or are not recommended for children As of late 2003, however, there have been few rigorous studies of antimigraine drugs in children; much more research is needed in this area Cyproheptadine, which is the drug most often prescribed for children’s migraines, is not always effective; preventive therapy with propranolol, one of the tricyclics, or an anticonvulsant medication appears to be safe as well as effective in children and adolescents PREGNANCY AND LACTATION Pregnancy and lactation complicate migraine treatment in that many antimigraine drugs should not be taken by pregnant or nursing women These include the ergot alkaloids, anticonvulsants, tricyclic antidepressants, methysergide, and the SSRIs In addition, NSAIDs should not be used during the last trimester of pregnancy OLDER ADULTS Some antimigraine medications are not recommended for patients over the age of 60–65, particularly the triptans and the ergot alkaloids Older adults may also be more susceptible to the side effects of NSAIDs and TCAs Patient dissatisfaction Antimigraine medications as a group have a high rate of reported patient complaints One reason is the high cost of some of these drugs; another is dosing difficulties One survey of migraine patients reported the following reasons for discontent with drug therapy: pain relief took too long (87%); pain was only partly relieved (84%); the medication sometimes failed to work (84%); headache returned within a day (71%); the drug had too many side effects (35%) Because of the limitations of antimigraine medications, many doctors advise their patients to supplement drug therapy with such other measures as adequate sleep and exercise, a low-fat diet, quitting smoking, stress management techniques, or cognitive-behavioral psychotherapy It is also worth noting that managed care (the health insurance industry) accounts for some patient dissatisfaction Most health plans strictly limit coverage to an “average” number of doses of triptans per month Patients who need more doses either must have their doctors try to get the insurance company to authorize them, or the patients must pay the full price of the extra medication themselves It is possible that new ways of thinking about migraine will lead to improved antimigraine medications in the future Migraine headaches are no longer regarded as “just headaches,” but as features of a largely inherited chronic disorder that increases the risk of long-term damage to the brain The use of MRIs and other new imaging techniques may eventually answer some unresolved questions about effective migraine treatment 76 Side effects Abortive medications In addition to the risk of rebound headaches, possible side effects of abortive medications include: • Triptans: May cause tingling, numbness, sensations of heat or flushing, dizziness, drowsiness, or pain at the injection site • Ergot alkaloids: May cause nausea, vomiting, diarrhea, weakness, itching, cold skin, thirst, tingling sensations, and severe muscle cramps; also may cause severe rebound headaches The most serious potential side effect of ergot alkaloids, however, is gangrene—the death of tissue in the fingers or toes due to constriction of the smaller blood vessels and loss of blood supply to the tissue • NSAIDs: May cause heartburn, nausea, and vomiting; may also cause drowsiness, dry mouth, or mild depression • Combination analgesics: Midrin has been reported to cause temporary dizziness and skin rashes The most common side effects of Fioricet and Fiorinal include lightheadedness, nausea, and sleep disturbances Also, the narcotics and barbiturates (Fiorinal) have the potential for drug abuse and dependence • Antiemetics: May cause anxiety, dizziness, low blood pressure, sedation, nausea, dry mouth, and restlessness Prophylactic medications The following side effects have been reported for prophylactic medications: • Anticonvulsants: Valproic acid may cause indigestion and vomiting, but hair loss, weight gain, tremor, hallucinations, and liver damage have also been reported Gabapentin and topiramate are associated with drowsiness, dizziness, tingling sensations, diarrhea, altered taste, and fatigue • Beta-blockers: May cause dizziness, fatigue, nausea, memory problems, sexual dysfunction, bradycardia (slowed heartbeat), and hallucinations • Calcium channel blockers: May cause low blood pressure and constipation; in addition, the headaches may grow worse for the first few weeks of treatment • TCAs: May cause dry mouth, constipation, difficulty urinating, increased appetite, loss of sexual desire, heavy sweating, agitation, tremor, and seizures • SSRIs: May cause loss of appetite or sexual desire, anxiety, drowsiness, nausea, or flulike symptoms • NSAIDs: More likely to cause digestive problems when used for prophylaxis than when used for acute treatment • Serotonin antagonists: Methysergide has been reported to cause insomnia, abdominal pain, diarrhea, nausea, GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS CAM preparations Feverfew should not be used by pregnant women because it may stimulate uterine contractions It may also cause mild acid indigestion in some people Patients who use fresh plant leaves rather than standardized preparations may experience mouth ulcers or temporary loss of taste Also, patients who use fresh plant leaves cannot regulate their doses: one time they may get too much of the drug and another time not enough The side effects reported for preparations made from butterbur root are rare, but include an unpleasant taste in the mouth, belching, and a mild skin rash in some patients Interactions Patients who are taking any antimigraine drug should make sure to give the doctor a list of all other medications that they take on a regular basis, including over-thecounter pain relievers, herbal preparations, and any special herbal or medicinal teas or extracts Abortive medications The following interactions have been reported for abortive medications: • Triptans: All the triptans narrow coronary arteries by 10–20% and will intensify the effects of other vasoconstrictive drugs, including the ergot alkaloids and drugs given for vascular disorders With the exception of naratriptan, the triptans cannot be taken together with MAO inhibitor antidepressants because of the risk of a rapid and dangerous rise in blood pressure Rizatriptan has been reported to interact with the beta-blocker propranolol • Ergot alkaloids: Cannot be taken together with the triptans Ergot alkaloids should not be taken together with methysergide because of an additive effect Should not be taken together with other vasoconstrictive drugs (including beta-blockers, some acid-reducing drugs, some antibiotics, and some antifungal drugs) because of the increased risk of gangrene • NSAIDs: These drugs tend to prolong bleeding time and should be used cautiously by patients taking blood-thinning medications Alcoholic beverages increase the risk of gastric ulcers or bleeding from the use of NSAIDs In addition, patients should not take more than one NSAID at a time • Combination analgesics: These drugs should not be used together with MAO inhibitors or other drugs that contain acetaminophen They will intensify the actions of other drugs that may cause drowsiness, including alcohol, TCAs, antihistamines, sedatives, and muscle relaxants • Antiemetics: Should not be taken together with alcohol (intensifies central nervous system depression), tricyclic antidepressants (lowers blood pressure), or phenobarbital Patients taking anticonvulsants may need to have their dosage increased if they are given an antiemetic Prophylactic medications The following interactions have been reported for prophylactic medications: • Anticonvulsants: Valproic acid will intensify the effects of other anticonvulsants, barbiturates, alcohol, and antidepressants It interacts with aspirin and heparin to increase the risk of spontaneous bleeding Gabapentin intensifies the effects of morphine, but is less effective when taken together with antacids • Beta-blockers: Antacids decrease the absorption of beta-blockers Cimetidine is reported to intensify the actions of beta-blockers Beta-blockers may interact with insulin or other diabetes medications to produce high blood sugar levels They should not be taken together with MAO inhibitors because of the risks of severe high blood pressure Cocaine also increases the risks of high blood pressure or other heart problems in patients taking beta-blockers • Calcium channel blockers: Verapamil may cause low blood pressure or dizziness if taken together with alcohol It should not be taken with beta-blockers because of a risk of congestive heart failure or slowed heartbeat Verapamil also intensifies the effects of cyclosporine and lithium • TCAs: Should not be taken together with barbiturates, alcohol, sleeping medicines, or sedatives because they intensify central nervous system depression They may also intensify the effects of certain antibiotics and antifungal medications They may interact with bupropion to produce seizures TCAs should never be taken with MAO inhibitors or SSRIs because of the risk of serotonin syndrome, a potentially fatal condition marked by fever, rapid changes in blood pressure, sweating, hyperreactive reflexes, delirium, nausea, vomiting, and coma Serotonin syndrome takes its name from the overly high levels of serotonin in the patient’s nervous system that are produced by these drug combinations • SSRIs: Should never be taken together with other antidepressant medications because of the risk of serotonin syndrome They may increase the patient’s drowsiness if taken together with antihistamines, sleep medications, opioid analgesics, and muscle relaxants Patients taking insulin or other diabetes medications may need to have their dosage adjusted if they are also taking an SSRI GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 77 Antimigraine medications heartburn, increased sensitivity to cold, and depression Cyproheptadine may cause dry mouth, increased appetite, and weight gain Antiparkinson drugs SSRIs should not be taken together with herbal preparations used as mild tranquilizers, particularly compounds containing valerian or St John’s wort • Serotonin antagonists: Methysergide should not be taken together with ergot alkaloids or triptans because it intensifies their vasoconstrictive action Patients taking this drug should give up smoking for the same reason In addition, methysergide has been reported to counteract the pain-relieving effectiveness of opioid analgesics CAM preparations Feverfew should not be used with anticoagulants (blood thinners), as it intensifies their effects It may also interfere with the body’s absorption of iron NSAIDs reduce the effectiveness of feverfew No interactions with prescription drugs have been reported for butterbur root preparations Sahai, Soma, MD, Robert Cowan, MD, and David Y Ko, MD “Pathophysiology and Treatment of Migraine and Related Headache.” eMedicine 30 April 2002 (May 9, 2004) Silberstein, S D., and P J Goadsby “Migraine: Preventive Treatment.” Cephalalgia 22 (September 2002): 491–512 Tepper, S J., and D Millson “Safety Profile of the Triptans.” Expert Opinion on Drug Safety (March 2003): 123–132 Victor, S., and S Ryan “Drugs for Preventing Migraine Headaches in Children.” Cochrane Database System Review (2003): CD002761 Waeber, C “Emerging Drugs in Migraine Treatment.” Expert Opinion on Emerging Drugs (November 2003): 437–456 OTHER Resources BOOKS “Headache.” Section 14, Chapter 168 in The Merck Manual of Diagnosis and Therapy, edited by Mark H Beers, MD, and Robert Berkow, MD Whitehouse Station, NJ: Merck Research Laboratories, 2002 Pelletier, Kenneth R., MD The Best Alternative Medicine, Part II, “CAM Therapies for Specific Conditions: Headache.” New York: Simon & Schuster, 2002 “Psychogenic Pain Syndromes.” Section 14, Chapter 167 in The Merck Manual of Diagnosis and Therapy, edited by Mark H Beers, MD, and Robert Berkow, MD Whitehouse Station, NJ: Merck Research Laboratories, 2002 Wilson, Billie Ann, RN, PhD, Carolyn L Stang, PharmD, and Margaret T Shannon, RN, PhD Nurses Drug Guide 2000 Stamford, CT: Appleton and Lange, 1999 PERIODICALS Corbo, J “The Role of Anticonvulsants in Preventive Migraine Therapy.” Current Pain and Headache Reports (February 2003): 63–66 Freitag, F G “Preventative Treatment for Migraine and Tension-Type Headaches: Do Drugs Having Effects on Muscle Spasm and Tone Have a Role?” CNS Drugs 17 (2003): 373–381 Kalin, P “The Common Butterbur (Petasites hybridus)— Portrait of a Medicinal Herb.” [in German] Forschende Komplementarmedizin und klassische Naturheilkunde 10 (April 2003) (Suppl 1): 41–44 Kruit, Mark C., MD, Mark A van Buchem, MD, PhD, Paul A M Hofman, MD, PhD, et al “Migraine as a Risk Factor for Subcortical Brain Lesions.” Journal of the American Medical Association 291 (January 28, 2004): 427–434 Malapira, Amelito, MD, and Jorge Mendizabal, MD “Migraine Headache.” eMedicine 22 September 2003 (May 9, 2004) 78 Punay, Nestor C., MD, and James R Couch, MD, PhD “Antidepressants in the Treatment of Migraine Headache.” Current Pain and Headache Reports (February 2003): 51–54 Cleveland Clinic Health System “Migraines in Children and Adolescents.” (May 9, 2004.) NINDS “Migraine Information Page.” NINDS, 2003 (May 9, 2004) ORGANIZATIONS American Council for Headache Education (ACHE) 19 Mantua Road, Mt Royal, NJ 08061 (856) 423-0258; Fax: (856) 423-0082 achehq@talley.com International Headache Society (IHS) Oakwood, Willowmead Drive, Prestbury, Cheshire SK10 4BU, United Kingdom +44 (0) 1625 828663; Fax: +44 (0) 1625 828494 rosemary@ihs.u-net.com National Headache Foundation 820 North Orleans, Suite 217, Chicago, IL 60610 (773) 525-7357 or (888) NHF-5552 U S Food and Drug Administration (FDA) 5600 Fishers Lane, Rockville, MD 20857-0001 (888) INFO-FDA (463-6332) Rebecca Frey, PhD S Antiparkinson drugs Definition Antiparkinson drugs are medicines used to reduce the symptoms of Parkinson’s disease GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Parkinson’s disease (PD) is a neurodegenerative disorder that affects movement In PD, cells in a part of the brain called the substantia nigra die off The normal function of these cells is to regulate the action of other cells in other brain regions by releasing a chemical called dopamine When substantia nigra cells release dopamine, the dopamine attaches to dopamine receptors on the other cells, which influences them in various ways depending on the specific type of cell The actions of these cells work in concert with other systems that influence movement When all cells are working properly together, the end result is controlled, fluid movement When substantia nigra cells die off, however, as they in PD, less dopamine is available for release Consequently, the cells that depend on receiving dopamine are not properly regulated The result is an imbalance in movement control that causes slowed movements, stiffness, and tremor—the classic signs of PD Antiparkinson drugs attempt to restore the balance through one of several mechanisms, depending on drug type The most effective drugs, called dopaminergic drugs, replace dopamine, or mimic its action in the brain Another group of drugs delays the breakdown of dopamine, thus increasing the level in the brain Other drugs act on the other systems that influence movement, preventing them from being too active Description Levodopa Levodopa, also called L-dopa, is the most widely prescribed antiparkinson medication; almost all PD patients eventually receive levodopa It is a chemical related to dopamine, and it is converted into dopamine within the brain Dopamine itself cannot cross the barrier between the bloodstream and the brain, while levodopa can This chemical form of dopamine works in the place of the natural dopamine that is lost due to the disease process Levodopa is chemically similar to amino acids, a type of molecule the body needs and absorbs from foods high in protein In the digestive system, a carrier picks up the levodopa and transports it into the bloodstream The same transport process occurs between blood and brain Meals high in protein may interfere with absorption of levodopa from the digestive tract or from the blood into the brain Patients may be advised to avoid high-protein meals too close to the time they take levodopa Once in the bloodstream, levodopa can be converted to dopamine This is a problem because, as noted, dopamine cannot be taken into the brain Additionally, dopamine in the periphery (that is, outside the brain) Key Terms Dopamine A neurotransmitter made in the brain that is involved in many brain activities, including movement and emotion Dyskinesia Impaired ability to make voluntary movements Orthostatic hypotension A drop in blood pressure that causes faintness or dizziness and occurs when an individual rises to a standing position Also known as postural hypotension Substantia nigra One of the movement control centers of the brain causes nausea, vomiting, and other adverse effects To minimize these side effects, levodopa is always given with another drug that inhibits its conversion to dopamine in the periphery In the United States, this drug is carbidopa Levodopa and carbidopa are available in a single tablet, with doses adjusted for maximum benefit However, it should be noted that peripheral dopamine is not always undesirable: it has important metabolic functions, including maintaining blood pressure Within the brain, levodopa is taken up by remaining substantia nigra cells, converted to dopamine, and released normally The extra dopamine provided by the levodopa allows the brain to maintain normal movements, even in the face of dying substantia nigra cells There are limitations because, as the disease progresses and more cells die, it becomes difficult for the few remaining cells to maintain normal function, even with extra dopamine Recommended dosage Levodopa treatment is usually started when the patient’s symptoms begin to interfere with daily living or the ability to work Initial dosage is typically 200–600 mg of levodopa per day, taken in tablets with carbidopa This amount of drug is contained in 2–6 tablets, which are taken at regular intervals during the day The dose is adjusted to the point at which symptoms are well controlled As the disease progresses, the dose is increased Precautions Levodopa itself is not well tolerated, which is why it is combined with carbidopa Carbidopa decreases peripheral metabolism of levodopa, which allows for lower doses of levodopa and less-severe side effects The combination is a safe and well-tolerated medication for patients with GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 79 Antiparkinson drugs Purpose Antiparkinson drugs Parkinson’s disease Levodopa may cause orthostatic hypotension, or low blood pressure upon standing Patients with low blood pressure or who are susceptible to orthostatic hypotension should be cautious when starting treatment or increasing the dose Levodopa can cause sudden and unexpected extreme drowsiness, which some physicians term “sleep attacks.” Currently, no reliable predictive criteria have been developed to determine which patients are susceptible Patients starting levodopa should be aware of this possibility, and discuss with their physician how best to modify their activities (such as driving) to guard against injury in the event of such an incident Patients who have had myocardial infarction (heart attack) or other heart abnormalities should be monitored carefully when beginning levodopa treatment Side effects Early on in the disease, levodopa can cause nausea, vomiting, orthostatic hypotension, and drowsiness Nausea and vomiting typically stop being problems within several months of treatment Long-term use of levodopa in PD often leads to dyskinesias, or unwanted and uncontrolled movements Dyskinesias appear as writhing, shaking, or twitching movements that may involve a small or large part of the body Early in the disease, lowering the dose of levopoda can help control dyskinesias, but later on, the lower dose leads to significant loss of movement Balancing the control of symptoms with the control of dyskinesias is a difficult and frustrating challenge for both patient and physician Long-term levodopa use can also lead to psychotic symptoms, including hallucinations, vivid and disturbing dreams, paranoia, and confusion meals are not a problem; and the effect of an individual dose lasts longer One of the most significant advantages of the dopamine agonists is their ability to delay the onset of dyskinesias when used instead of levodopa at the start of disease Patients who take a dopamine agonist instead of levodopa for the first 1–2 years tend to develop dyskinesias many months later than those who begin on levodopa On the other hand, dopamine agonists are not quite as effective as levodopa at controlling other PD symptoms, and may cause more confusion in elderly patients For this reason, common advice for elderly patients is to begin on levodopa, with the expectation that dyskinesias are less likely to be a serious problem within the treatment timeframe, while younger patients should begin on a dopamine agonist to delay dyskinesias within a much longer timeframe of treatment Dopamine agonists prescribed for PD in the United States include pramipexole, ropinirole, pergolide, and bromocriptine Approval of another, apomorphine, was expected in early 2004 Unlike the others, apomorphine is injected and has a very short duration of action It is intended for intermittent (not continuous) use as a treatment for emergent symptoms while waiting for the effect of other medications to begin Recommended dosage There are half a dozen dopamine agonists available in oral forms for treatment of PD The individual dosage and schedule for each vary In each case, a low dose is used to begin with, with a gradual adjustment over several weeks to achieve the optimum level of symptomatic benefit Precautions Like levodopa, the dopamine agonists may cause sudden and unpredictable episodes of extreme drowsiness Interactions Patients who are taking drugs called nonselective MAO (monoamine oxidase) inhibitors should discontinue these drugs at least two weeks before beginning levodopa MAO inhibitors are used to treat depression A selective MAO-B inhibitor, such as selegiline, may be taken, and indeed is often prescribed for use in Parkinson’s disease Description Dopamine agonists Long-term use of dopamine agonists can cause nausea, vomiting, orthostatic hypotension, and psychotic symptoms, including hallucinations, vivid and disturbing dreams, paranoia, and confusion While the risk for developing dyskinesias is lower with dopamine agonists, their long-term use does lead to this complication in many patients Description Dopamine agonists are drugs that mimic the effect of dopamine by stimulating the same cells as dopamine They have several theoretical advantages over levodopa in the treatment of PD: dopamine agonists not require uptake and release by substantia nigra cells; they not compete with amino acids for transport, and so high-protein 80 Side effects COMT inhibitors COMT (Catechol-O-MethylTransferase) inhibitors restrict the action of an enzyme that converts levodopa to dopamine in the periphery (outside the brain) This allows more of the levodopa to reach the brain In this way, a GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Recommended dosage There are two COMT inhibitors approved for use in PD Entacapone is dosed at 200 mg with each dose of levodopa Tolcapone is dosed at either 100 or 200 mg three times per day Precautions Tolcapone has been associated with liver damage in a small number of patients, which has led to death in three patients Tolcapone is only approved for use by patients for whom other therapies are not providing adequate relief of symptoms COMT inhibitors increase the effectiveness of levodopa, as well as levodopa’s side effects Consequently, the same precautions apply for use of COMT inhibitors as for levodopa fermented beverages such as beer or wine, and smoked or pickled meats This effect is also seen very rarely in patients taking the recommended dose for PD Selegiline should not be used with meperidine Use with other narcotics should only be with the express approval of the patient’s physician Side effects Selegiline can cause side effects similar to levodopa, and when taken with levodopa, may worsen those effects No reports of sudden drowsiness have been published for PD patients on selegiline alone Interactions Interaction between selegiline and certain kinds of antidepressants is possible, and patients should consult with their physician before combining these two types of medications Description Side effects COMT inhibitors can cause diarrhea They also can increase the severity of levodopa’s side effects, including orthostatic hypotension, hallucinations, and dyskinesias Description MAO-B inhibitors MAO-B inhibitors restrict the action of monoamine oxidase B, an enzyme that breaks down levodopa in the brain Thus, an MAO-B inhibitor prolongs the effectiveness of dopamine, as well as a dose of levodopa The only MAO-B inhibitor in widespread use for Parkinson’s disease is selegiline, also called deprenyl Selegiline is often used in the early stages of PD, before other drugs, based on its mild symptomatic benefit It is also often prescribed based on the possibility it may be neuroprotective—that is, it may help slow the death of neurons (brain cells) in the substantia nigra While some experiments have suggested this may be true, others have shown no effect, and as of late 2003, there was no widespread consensus that selegiline had any effect in PD other than on symptoms Amantadine Amantadine is prescribed for two different purposes in PD It has a mild symptomatic effect in early PD, and is often prescribed before levodopa for that reason It also reduces dyskinesias, and may be prescribed late in the disease once this symptom develops Recommended dosage Amantadine is dosed at 200–300 mg per day Precautions Patients with kidney disease or reduced kidney function require a much lower dose of amantadine Side effects Amantadine can cause side effects similar to levodopa, including hallucinations, confusion, and orthostatic hypotension Amantadine can also cause mottled skin and swelling in the peripheral tissues such as the legs Description Recommended dosage Anticholinergics Selegiline is usually prescribed at mg twice daily Precautions At doses higher than those used in PD, selegiline in combination with certain foods can lead to dangerously high blood pressure These foods include aged cheeses, Anticholinergics were the first class of antiparkinson medications developed, but are used much less now than in the past, due to the availability of improved drugs Anticholinergics suppress activity of the acetylcholine system in the brain, which is relatively overactive in PD They are GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 81 Antiparkinson drugs COMT inhibitor increases the effectiveness of a dose of levodopa A COMT inhibitor cannot be used by itself, but must be administered with levodopa Antiviral drugs Key Terms Asthenia muscle weakness Cytomegalovirus (CMV) A type of virus that attacks and enlarges certain cells in the body The virus also causes a disease in infants studies, or adverse fetal effects in animal studies, but no available human data Category D: Evidence of fetal risk, but benefits outweigh risks Category X: Evidence of fetal risk Risks outweigh any benefits Herpes simplex A virus that causes sores on the lips (cold sores) or on the genitals (genital herpes) Prophylactic Guarding from or preventing the spread or occurrence of disease or infection HIV Acronym for human immunodeficiency virus, the virus that causes AIDS Retrovirus A group of viruses that contain RNA and the enzyme reverse transcriptase Many viruses in this family cause tumors The virus that causes AIDS is a retrovirus Parkinsonism A group of conditions that all have these typical symptoms in common: tremor, rigidity, slow movement, and poor balance and coordination Pregnancy category A system of classifying drugs according to their established risks for use during pregnancy Category A: Controlled human studies have demonstrated no fetal risk Category B: Animal studies indicate no fetal risk, but no human studies, or adverse effects in animals, but not in well-controlled human studies Category C: No adequate human or animal mainly effective against tremor and rigidity, and less so against slowed movements Shingles An disease caused by an infection with the Herpes zoster virus, the same virus that causes chicken pox Symptoms of shingles include pain and blisters along one nerve, usually on the face, chest, stomach, or back Virus A tiny, disease-causing structure that can reproduce only in living cells and causes a variety of infectious diseases ORGANIZATIONS National Parkinson Foundation 1501 N.W 9th Avenue, Miami, FL 33136-1494 (800) 327-4545 mailbox@parkinson.org Recommended dosage Different anticholinergics are dosed at different levels and frequencies A dose is chosen that maximizes benefits and minimizes side effects The dose is gradually increased to avoid worsening side effects Side effects Anticholinergics can cause significant confusion, delirium, and hallucinations, especially in older patients For this reason, they are seldom used in this group They can also cause constipation and urinary retention Richard Robinson S Antiviral drugs Definition Antiviral drugs are medicines that cure or control virus infections Purpose Resources Antivirals are used to treat infections caused by viruses Unlike antibacterial drugs, which may cover a wide range of pathogens, antiviral agents tend to be narrow in spectrum, and have limited efficacy PERIODICAL Olanow, C W., R L Watts, and W C Koller, eds “An Algorithm (Decision Tree) for the Management of Parkinson’s Disease (2001): Treatment Guidelines.” Neurology 56, Supplement (June 12, 2001): S1–S88 Description WEBSITE Parkinson’s Disease: Etiology, Diagnosis and Management— Version 2.2 November 6, 2003 (March 2, 2004) 82 Exclusive of the antiretroviral agents used in HIV (AIDS) therapy, there are currently only 11 antiviral drugs available, covering four types of virus Acyclovir (Zovirax), famciclovir (Famvir), and valacyclovir (Valtrex) are GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Amantadine (Symmetrel), oseltamivir (Tamiflu), rimantidine (Flumadine), and zanamivir (Relenza) are useful in treatment of the influenza virus Amantadine, rimantadine, and oseltamivir may be administered throughout the flu season as preventatives for patients who cannot take influenza virus vaccine Cidofovir (Vistide), foscarnet (Foscavir), and ganciclovir (Cytovene) have been beneficial in treatment of cytomegalovirus in immunosupressed patients, primarily HIV-positive patients and transplant recipients Ribavirin (Virazole) is used to treat respiratory syncytial virus In combination with interferons, ribavirin has shown some efficacy against hepatitis C, and there have been anecdotal reports of utility against other types of viral infections As a class, the antivirals are not curative, and must be used either prophylactically or early in the development of an infection Their mechanism of action is typically to inactivate the enzymes needed for viral replication This will reduce the rate of viral growth, but will not inactive the virus already present Antiviral therapy must normally be initiated within 48 hours of the onset of an infection to provide any benefit Drugs used for influenza may be used throughout the influenza season in high risk patients, or within 48 hours of exposure to a known carrier Antiherpetic agents should be used at the first signs of an outbreak Anti-cytomegaloviral drugs must routinely be used as part of a program of secondary prophylaxis (maintenance therapy following an initial response) in order to prevent reinfection in immunocompromised patients Recommended dosage Dosage varies with the drug, patient age and condition, route of administration, and other factors See specific references Precautions Ganciclovir is available in intravenous injection, oral capsules, and intraoccular inserts The capsules should be reserved for prophylactic use in organ transplant patients, or for HIV infected patients who cannot be treated with the intravenous drug The toxicity profile of this drug when administered systemically includes granulocytopenia, anemia, and thrombocytopenia The drug is in pregnancy category C, but has caused significant fetal abnormalities in animal studies including cleft palate and organ defects Breast-feeding is not recommended Cidofovir causes renal toxicity in 53% of patients Patients should be well hydrated, and renal function should be checked regularly Other common adverse effects are nausea and vomiting in 65% or patients, asthenia in 46% and headache and diarrhea, both reported in 27% of cases The drug is category C in pregnancy, due to fetal abnormalities in animal studies Breast-feeding is not recommended Foscarnet is used in treatment of immunocompromised patients with cytomegalovirus infections and in acyclovir-resistant herpes simples virus The primary hazard is renal toxicity Alterations in electrolyte levels may cause seizures Foscarnet is category C during pregnancy The drug has caused skeletal abnormalities in developing fetuses It is not known whether foscarnet is excreted in breast milk, however the drug does appear in breast milk in animal studies Valaciclovir is metabolized to acyclovir, so that the hazards of the two drugs are very similar They are generally well tolerated, but nausea and headache are common adverse effects They are both pregnancy category B Although there have been no reports of fetal abnormalities attributable to either drug, the small number of reported cases makes it impossible to draw conclusions regarding safety in pregnancy Acyclovir is found in breast milk, but no adverse effects have been reported in the newborn Famciclovir is similar in actions and adverse effects Ribavirin is used by aerosol for treatment of hospitalized infants and young children with severe lower respiratory tract infections due to respiratory syncytial virus (RSV) When administered orally, the drug has been used in adults to treat other viral diseases including acute and chronic hepatitis, herpes genitalis, measles, and Lassa fever, however there is relatively little information about these uses In rare cases, initiation of ribavirin therapy has led to deterioration of respiratory function in infants Careful monitoring is essential for safe use The anti-influenza drugs are generally well tolerated Amantadine, which is also used for treatment of Parkinsonism, may show more frequent CNS effects, including sedation and dizziness Rapid discontinuation of amantidine may cause an increase in Parkinsonian symptoms in patients using the drug for that purpose All are schedule C for pregnancy In animal studies, they have caused fetal malformations in doses several times higher than the normal human dose Use caution in breast-feeding Interactions Consult specific references for information on drug interactions Use particular caution in HIV-positive patients, since these patients are commonly on multi-drug regimens with GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 83 Antiviral drugs effective against the herpes virus, including herpes zoster and herpes genitalis They may also be of value in either conditions caused by herpes, such as chicken pox and shingles These drugs are not curative, but may reduce the pain of a herpes outbreak and shorten the period of viral shedding Anxiolytics Key Terms Amygdala An almond-shaped area of the brain involved with coordinating mood, feeling, instinct, and memory Buspirone An anxiolytic drug that does not affect GABA, but instead modifies serotonin neurotransmission Unlike benzodiazepines, it may take 3–6 weeks for buspirone to reach maximal effectiveness As a result, the drug is only used to treat generalized anxiety disorder Generalized anxiety disorder An anxiety disorder characterized by excessive worry or fear about a number of activities or events Neurotransmitter A chemical in the brain that transmits messages between neurons, or nerve cells Panic disorder A series of unexpected attacks, involving an intense, terrifying fear similar to that caused by a life-threatening danger Phobic disorder Persistent fear of social situations, objects, or specific situations Selective serotonin reuptake inhibitors (SSRIs) Prescription drugs used as antidepressants and anti-anxiety agents that enhance the actions of the neurotransmitter serotonin a high frequency of interactions Ganciclovir should not be used with other drugs which cause hematologic toxicity, and cidofovir should not be used with other drugs that may cause kidney damage the trade name of Ativan, and alprazolam, sold under the brand name of Xanax Resources Diazepam and other anxiolytics reduce the frequency, severity, and duration of anxiety symptoms in individuals who have medical or psychiatric disorders associated with anxiety Illnesses associated with anxiety symptoms include heart disease, gastrointestinal diseases, as well as diseases that affect the lungs and make breathing difficult Anxiety may also occur in the absence of these diseases and is thought to involve abnormal function of several different neurotransmitters in a region of the brain known as the amygdala The amygdala plays a critical role in assessing fear and responding to danger Examples of common anxiety disorders include generalized anxiety disorder, panic disorder, and phobic disorders Nearly 25% of the population will develop an anxiety disorder at some time during their life PERIODICALS Gray, Mary Ann “Antiviral Medications.” Orthopaedic Nursing 15 (November-December 1996): 82 Samuel D Uretsky, PharmD S Anxiolytics Definition Anxiolytics are prescription drugs used to treat and prevent anxiety disorders Anxiety is an emotional state in which fear dominates a person’s life Drugs that are often prescribed to manage anxiety episodes are known as benzodiazepines Probably the best-known example of a benzodiazepine is the anxiolytic diazepam In the United States, diazepam is sold under the brand name Valium All together, there are six other anxiolytics approved for use in the United States All of these medications are similar to diazepam in their chemical structures and the way they exert their beneficial anxiolytic effects However, these drugs differ from one another in several important ways Some drugs work faster than others, while other drugs continue their anxiolytic effects for longer periods of time Additionally, some anxiolytics differ from one another in the way that they are eliminated from the body, and others are involved with more drug-to-drug interactions than others In 2002, the two most commonly prescribed anxiolytics were the drugs lorazepam, sold under 84 Purpose Description Benzodiazepine anxiolytics like diazepam have similar chemical structures, including a benzene ring fused to a diazepine ring This structure is important for anxiolytic activity In the brain, anxiolytics are believed to enhance the actions of gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter By enhancing GABA’s inhibitory actions, brain cells are unable to be stimulated by excitatory neurotransmitters, and this inhibition alleviates symptoms of anxiety Although benzodiazepines like diazepam alleviate symptoms of anxiety in a manner similar to older anxiolytics like barbiturates, the distinctive feature that sets benzodiazepines apart from barbiturates is the wide margin of GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Recommended dosage The usual adult dosage of diazepam is 2–10 mg taken by mouth two to four times a day In addition to oral tablets, diazepam is also available as an oral liquid or as an injection that can be given either intramuscularly or intravenously to individuals with severe anxiety symptoms Dosages for anxiolytics that are chemically related to diazepam vary Examples include alprazolam given by mouth in dosages of 0.25–0.5 mg three times a day, or lorazepam taken by mouth in dosages of 0.5–2 mg two or three times a day The anxiolytic effects of diazepam occur in as little as 15 minutes, but only last for two or three hours These features make diazepam an ideal drug for quickly eliminating acute anxiety attacks On the other hand, lorazepam’s anxiolytic effects are a little slower in onset but tend to persist for more than six hours As a result, lorazepam may be better suited to prevent anxiety in people with generalized anxiety disorder Elderly patients may be more sensitive to the side effects of diazepam and related anxiolytics than younger adults As a result, initial doses are usually reduced and increased slowly in the elderly to avoid excessive sedation and other unwanted side effects Precautions Paradoxically, excitement, rage, anger, or hostility may occur in individuals taking anxiolytics for their calming effects These reactions may occur secondarily to the relief of anxiety and usually occur within the first two weeks of therapy If these reactions occur, anxiolytic therapy should be stopped Because suicidal tendencies may be present in patients who also have accompanying depressive disorders, only small amounts of anxiolytic agents should be dispensed at any given time to minimize the likelihood of intentional drug overdoses Side effects Diazepam and related anxiolytics are often associated with drowsiness, sedation, confusion, and difficulty maintaining balance These effects are more pronounced at the beginning of therapy and after dosage increases People should avoid driving or performing tasks that require alertness until they know how the drugs will affect them When using anxiolytics like diazepam, fainting or dizziness sometimes occurs when a person stands up suddenly Blurred vision may also occur When anxiolytics are used in high doses or taken with other drugs that depress the actions of the brain, such as alcohol or barbiturates, the normal breathing responses of the body may be interrupted and patients may stop breathing For this reason, alcohol and other CNS depressants should be avoided in people taking diazepam and related anxiolytics It is also best to avoid anxiolytics in those persons with a prior history of drug abuse or those who are suicidal Withdrawal symptoms will occur if patients stop taking anxiolytics suddenly Patients should only discontinue using diazepam and related anxiolytics at the advice of their physician and the dosage of the drugs should be reduced slowly to avoid withdrawal effects Interactions Diazepam will increase the drowsiness or sedative effects of other central nervous system depressants like alcohol or barbiturates These combinations should be avoided Certain drugs, especially those eliminated by the liver, may interfere with the elimination of diazepam from the body Anticonvulsants, antidepressants, numerous antibiotics, and cimetidine inhibit the elimination of most GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 85 Anxiolytics safety associated with benzodiazepines Unlike barbiturates, benzodiazepine anxiolytics have a wide margin of safety, meaning that the doses of benzodiazepines that cause life-threatening toxicities are considerably larger than the doses that are normally used for alleviating anxiety Diazepam and related anxiolytics are safe and effective medications for alleviating anxiety symptoms Until the 1990s, these drugs were the mainstay of pharmacologic treatment for anxiety-related disorders However, these anxiolytics possess some unwanted properties For example, the Drug Enforcement Administration (DEA) classifies diazepam and related anxiolytics as controlled substances because the drugs are sometimes abused, or used for recreational purposes due to their desirable anxiolytic effects Additionally, physical dependence develops when these medications are used at high doses or for prolonged periods of time This means that people experience unpleasant withdrawal symptoms if they abruptly stop taking their medication Common withdrawal symptoms include anxiety, insomnia, restlessness, agitation, muscle tension, and irritability, although seizures and depression may sometimes occur The unpleasant withdrawal effects that are experienced when discontinuing these medications cause people to continue using the drugs to avoid unpleasant effects Because these drugs are sometimes used for non-medicinal purposes and are associated with unpleasant withdrawal symptoms, benzodiazepine anxiolytics are now typically prescribed only for short-term treatment of anxiety disorders, until other anxiolytics like buspirone or selective serotonin reuptake inhibitors (SSRIs) begin working Aphasia anxiolytics from the body, causing higher blood levels and increased side effects Resources States with aphasia, and roughly 100,000 new cases occur each year There are more people with aphasia than with Parkinson’s disease, cerebral palsy, or muscular dystrophy BOOKS Drug Facts and Comparisons, 6th edition St Louis, MO: A Wolter Kluwer Company, 2002 Kirkwood, Cynthia A Anxiety Disorders Pharmacotherapy: A Pathophysiologic Approach, edited by Joseph T Dipiro, et al Stamford, CT: Appleton and Lange, 1999 Mosby’s Medical Drug Reference St Louis, MO: Mosby, 1999 Kelly Karpa, PhD, RPh S Aphasia Definition Aphasia is a communication disorder that occurs after language has been developed, usually in adulthood Not simply a speech disorder, aphasia can affect the ability to comprehend the speech of others, as well as the ability to read and write In most instances, intelligence per se is not affected Description Aphasia has been known since the time of the ancient Greeks However, it has been the focus of scientific study only since the mid-nineteenth century Although aphasia can be caused by a head injury and neurologic conditions, its most common cause is stroke, a disruption of blood flow to the brain, which affects brain metabolism in localized areas of the brain The onset of aphasia is usually abrupt, and occurs in individuals who have had no previous speech or language problems Aphasia is at its most severe immediately after the event that causes it Although its severity commonly diminishes over time through both natural, spontaneous recovery from brain damage and from clinical intervention, individuals who remain aphasic for two or three months after its onset are likely to have some residual aphasia for the rest of their lives However, positive changes often continue to occur, largely with clinical intervention, for many years The severity of aphasia is related to a number of factors, including the severity of the condition that brought it about, general overall health, age at onset, and numerous personal characteristics that relate to motivation Demographics The National Aphasia Association estimates that approximately 25–40% of stroke survivors develop aphasia There are approximately one million persons in the United 86 Causes and symptoms Although aphasia occasionally results from damage to subcortical structures such as basal ganglia or the thalamus that has rich interconnections to the cerebral cortex, aphasia is most frequently caused by damage to the cerebral cortex of the brain’s left hemisphere This hemisphere plays a significant role in the processing of language skills However, in about half of left-handed individuals (and a few right-handed persons), this pattern of dominance for language is reversed, making right-hemisphere damage the cause of aphasia in this small minority Because the left side of the brain controls movement on the right side of the body (and vice versa), paralysis affecting the side of the body opposite the side of brain damage is a frequent co-existing problem This condition is called hemiplegia and can affect walking, using one’s arm, or both If the arm used for writing is paralyzed, it poses an additional burden on the diminished writing abilities of some aphasic individuals If paralysis affects the many muscles involved in speaking, such as the muscles of the tongue, this condition is called dysarthria Dysarthria often co-occurs with aphasia There are a few more problems that can result from the same brain injury that produces aphasia, and complicate its presentation Most notable among them are the problems collectively called apraxia, which influences one’s ability to program movement Apraxic difficulties make voluntary movements difficult and hard to initiate Apraxia of speech results in difficulty initiating speech and in making speech sounds consistently It frequently co-occurs with both dysarthria and aphasia Finally, sensory problems such as visual field deficits (specifically, hemianopsia) and changes in (or absence of) sensation in arms, legs, and tongue commonly occur with aphasia There are neurological disorders other than aphasia that also manifest difficulty with language This makes it important to note what aphasia is not Traumatic brain injury and dementias such as Alzheimer’s disease are excellent examples Although brain injury is a cause of aphasia, most head injuries produce widespread brain damage and result in other neuropsychological and cognitive disorders These disorders often create language that is disturbed in output and form, but are typically the linguistic consequences of cognitive disturbances In Alzheimer’s disease, the situation is much the same Language spoken by individuals with Alzheimer’s reflect their cognitive problems, and, as such, differ from the language retrieval problems typically designated as aphasia In GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Nonfluent aphasia Frontal cortex is responsible for shaping, initiating, and producing behaviors Individuals with nonfluent aphasia characteristically have brain damage affecting Broca’s area of the cortex and the frontal brain areas surrounding it These areas are responsible for formulating sound, word, and sentence patterns Damage to the anterior speech areas results in slow, labored speech with limited output and prosody and difficulty in producing grammatical sentences Because the motor cortex is closely adjacent, nonfluent Broca’s aphasia, by far the most common nonfluent variant, is quite likely to co-occur with motor problems Damage to these areas of the brain can cause types of aphasia (Illustration by Electronic Illustrators Group.) short, if the damage that results in language problems is general and produces additional intellectual problems, then aphasia is a correct diagnosis In the absence of other significant intellectual problems, then the language disorder is probably localized to the brain’s language processing areas and is properly termed aphasia Finally, aphasia is not conventionally used to refer to the developmental language learning problems encountered by some atypically developing children However, when children who have been previously developing language normally have a stroke or some other type of localized brain damage, then the aphasia diagnosis is appropriate Aphasia manifests different language symptoms and syndromes as a result of where in the language-dominant hemisphere the damage has occurred The advent of neuroimaging has improved the ability to localize the area of brain damage Nevertheless, the different general patterns of language strengths and weaknesses, as well as unexpected dissociations in language function, can explain how normal language is processed in the brain, as well as provide insights into intervention for aphasia Aphasic individuals almost uniformly have some difficulty in using the substantive words of their native language Most experts in aphasia recognize that aphasia varies along two major dimensions: auditory comprehension ability and fluency of speech output In reality, aphasic behaviors vary greatly from individual to individual, Several additional characteristics of nonfluent aphasia can be noted: in nonfluent aphasia verbs and prepositions are disproportionately affected; speech errors occur mostly at the level of speech sounds, producing sound transpositions and inconsistencies; auditory comprehension is only minimally affected; reading abilities parallel comprehension, writing problems parallel speech output, but are sometimes further complicated by hemiplegia; finally, there is an inability to repeat what someone else says Fluent aphasia Fluent aphasias occur when damage occurs in the posterior language areas of the brain, where sensory stimuli from hearing, sight, and bodily sensation converge In fluent aphasia, the prosody and flow of speech is maintained; one typically must listen closely to recognize that the speech is not normal Because this posterior damage is located far from the motor areas in the frontal lobes, individuals with fluent aphasia seldom have co-existing difficulty with the mechanics of speech, arm use, or walking There are three major variants of fluent aphasia, each thought to occur as a function of disruption to different posterior brain regions WERNICKE’S APHASIA Wernicke’s aphasia results from temporal lobe damage, where auditory input to the brain is received The essential characteristic is that individuals with this disorder have disproportionate difficulty in understanding spoken and written language They also have problems comprehending and monitoring their own speech They are often verbose, and frequently use inappropriate and even jargon words when they speak Reading and writing are impaired in similar ways to auditory comprehension and speech output Their comprehension difficulties preclude their being able to repeat others’ words ANOMIC APHASIA Most people, particularly as they grow older, have trouble with the names of persons and GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 87 Aphasia and fluctuate in a given individual as a result of fatigue and other factors In addition, largely in relationship to lesion size, aphasias differ in overall severity Aphasia things; all aphasic persons experience these difficulties But when brain damage occurs in the area of the posterior brain where information from temporal, parietal, and occipital lobes converge, this problem of naming is much more pervasive than for normal and aphasic speakers alike Most anomic aphasic individuals have excellent auditory comprehension and read well But for most of them, writing mirrors speech, and individuals with anomic aphasia can take advantage of words provided by others Hence, their repetition ability is good Although anomic aphasia is classified as a fluent syndrome, frequent stops, starts, and word searches typically make speech choppy in between runs of fluency CONDUCTION APHASIA Individuals with conduction aphasia are thought to have a discrete brain lesion that disrupts the pathways that underlie the cortex and connect the anterior and posterior speech regions These individuals have good comprehension, as well as high awareness of the errors that they make Placement of their brain damage also suggests that there should be little interference with speech production, reading, and writing However, damage to the neural links between posterior and anterior speech areas makes it quite difficult for these individuals to correct the errors they hear themselves making Conduction aphasia also affects the ability to repeat the speech of others or to take advantage of the cues others provide The speech of individuals with this problem includes many inappropriate words, typically involving inappropriate sequences of sounds UNUSUAL APHASIA SYNDROMES There are a few other rare aphasic syndromes (called “transcortical aphasias”) and unique dissociations in aphasic patterns The above aphasias represent the most common distinctive syndromes However, they are estimated to account for only approximately 40% of individuals with aphasia MIXED AND GLOBAL APHASIA The remaining majority, about 60% of aphasic individuals, have aphasias that result from brain lesions involving both the anterior and posterior speech areas Their aphasias, thus, affect both speech production and comprehension They frequently have reading and writing disorders as well Individuals with mixed and global aphasia are also very likely to have hemiplegia and dysarthria, as well as a variety of sensation losses Depending upon the severity of these symptoms, people with mild-to-moderate symptomatology of this type are said to have mixed aphasia; global aphasia describes individuals with extensive difficulties in all language skills Diagnosis As an aid to accurate diagosis immediately following stroke, it is important to differentiate aphasia from cognitive disorders such as confusion and disorientation To this 88 end, brief, but general testing of the language functions (naming, comprehension, reading, writing, and repetition) can be incorporated into broader testing that might determine other cognitive functions Evaluators must remember that language is the medium though which most of these other functions are observed Therefore, language should be assessed first; if extensive aphasia is present, then only cautious interpretations of other cognitive functions may be given At present, there are few available objective and standardized measures for testing during the acute phases of disorders such as stroke A number of standardized measures are available that provide an inventory of aphasic symptoms These tests are useful in providing baseline and follow-up assessments to measure progress in treatment, as well as to guide the treatment itself A fairly general feature of aphasia tests is that individuals without aphasic symptoms should perform with almost no errors on them Tests are available to measure the extent and severity of language impairments as well as to provide information about functional skills and outcomes Finally, there are assessments designed specifically to look at quality of life with aphasia Treatment team Because of the various other problems in addition to language that affect most individuals with aphasia, a multidisciplinary team is used in rehabilitation centers for the management of aphasia Team members, as well as speech-language pathologists, typically include physical and occupational therapists, clinical neuropsychologists, nurses, and social workers who are guided by physiatrists and neurologists Once discharged from rehabilitation centers, aphasic individuals often continue their treatment by speech-language pathologists in settings such as speech and hearing clinics Self-help groups and support via the Internet are available as well Treatment Most individuals with aphasia are hospitalized for some period of time for treatment of the condition that has resulted in aphasia Assessment of the extent and type of language disorder is made during that time, as assessment of the ability to swallow (dysphagia) Early medical intervention is important for lessening the long-term effects of stroke Recovery and rehabilitation To date, no pharmacological treatments for aphasia have proven effective, although a number of drugs (dopaminergic, cholinergic, and neurotrophic) continue to be investigated, usually in conjunction with behavioral treatments for aphasia Various behavioral treatment approaches for aphasia exist They are usually characterized GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS Clinical trials Randomized control trials (RCTs) are rare for the behavioral realm of treatments Aphasia is no exception To date, only four RCTs have been completed, with three of the four addressing to the efficacy of treatment A far greater number of phases I and II studies exist, and investigate the value of language intervention, particularly post stroke The largest testimony comes from single-case designs and qualitative case studies that agree that treatment has a positive influence on outcome Only one meta-analysis of significant scope has been completed (Robey, 1998) Prognosis The traditional view is that most of the language gains made by aphasic individuals will occur in the first six months following injury, except in persons with global aphasia, who may begin the recovery process later, but are shown to make gains through one year Significantly, it must be noted that most traditional treatment techniques have been validated using aphasic patients whose period of spontaneous recovery has passed Some people with aphasia may be able to return to work, although the communicative demands of many occupations may affect employment As of the late 1990s, research has begun to focus on recovery across the remainder of the lifespan, and it has become apparent that aphasic individuals continue to make progress, often for years after the precipitating event The factors that explain very late recovery are not clear and will require scientific observation and study Special concerns Despite the prevalence of aphasia, the disorder is neither well recognized nor well understood Aphasia’s psychosocial and vocational consequences are overwhelmingly devastating, but community understanding is at best limited Similarly, despite substantial evidence concerning the effectiveness of intervention, skepticism about the value of treatment remains As a consequence of both of these factors, many aphasic individuals and their families are not well informed about either the disorder or what might be done to alleviate it Additionally, although a significant and growing number of individuals in the United States is bilingual, there is a surprising lack of research concerning the effects of speaking more than one language on recovery from aphasia Finally, current funding for only very limited treatment for aphasia is available via third-party reimbursement Resources BOOKS Davis, G A Aphasology: Disorders and Clinical Practice Boston: Allyn and Bacon, 2000 Goodglass, H Understanding Aphasia New York: Academic Press, 1993 Hillis, A E The Handbook of Adult Language Disorders New York: Psychology Press, 2002 PERIODICALS Robey, R R “A Meta-analysis of Clinical Outcomes in the Treatment of Aphasia.” Journal of Speech and Hearing Research 41 (1998): 172–187 ORGANIZATIONS Aphasia Hope Foundation 2436 West 137th St., Leawood, KS 66224 (913) 402-8306 or (866) 449-5894; Fax: (913) 402-8315 National Aphasia Association 29 John Street, New York, NY 10038 (212) 267-2812 or (800) 922-4622 naa@ aphasia.org Audrey L Holland, PhD Apolipoprotein B deficiency see BassenKornzweig syndrome S Apraxia Definition Apraxia is a neurological disorder In general, the diagnostic term “apraxia” can be used to classify the inability of a person to perform voluntary and skillful movements of one or more body parts, even though there GALE ENCYCLOPEDIA OF NEUROLOGICAL DISORDERS 89 Apraxia dichotomously as restorative (restitutive) or compensatory The goal of restorative treatments is to reestablish disordered language skills Goals for compensatory approaches are to develop and train alternative approaches to circumvent the language skills that have been affected by aphasia Most clinicians use both approaches (often simultaneously) to aid in language recovery Some examples of restorative approaches include practice of carefully selected syntactic structures, naming drills, or practice using self-selected communication needs such as using the telephone Compensatory approaches include training conversational partners to modify their own language and communication skills in ways that make it easier for the aphasic individual to communicate, or teaching aphasic individuals to use a relatively intact language skill such as writing or drawing to substitute for talking Computerized approaches to both restitutive and compensatory aphasia treatment are increasing Many clinics offer both individual treatment and group treatment, with the latter offering increased psychosocial support Many clinics also incorporate family support groups ... SK10 4BU, United Kingdom +44 (0) 16 25 828 663; Fax: +44 (0) 16 25 828 494 rosemary@ihs.u-net.com National Headache Foundation 820 North Orleans, Suite 21 7 , Chicago, IL 60 610 ... Leawood, KS 66 21 1 -2 6 72 ( 913 ) 9066000 fp@aafp.org American Academy of Neurology 10 80 Montreal Avenue, St Paul, Minnesota 5 511 6 (6 51) 695 -1 9 40; Fax: (6 51) 69 527 91 info@aan.org... University Press, 19 97 Muscular Dystrophy Association 3300 East Sunrise Drive, Tucson, AZ 85 718 -3 20 8 ( 520 ) 52 9 -2 000 or (800) 57 21 7 17; Fax: ( 520 ) 52 9-5 300 WEBSITES ALS Society of Canada